Department of Pathophysiology, School of Medicine, Nantong University, Nantong, Jiangsu 226000, PR China.
Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Soochow University, Suzhou, Jiangsu 215123, PR China; 2011 Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215123, PR China.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188558. doi: 10.1016/j.bbcan.2021.188558. Epub 2021 Apr 29.
Increasing evidence shows that numerous cancer-testis antigens (CTAs) are uniquely overexpressed in various types of cancer and most CTAs are oncogenic. Overexpression of oncogenic CTAs promotes carcinogenesis, cancer metastasis, and drug resistance. Oncogenic CTAs are generally associated with poor prognosis in cancer patients and are an important hallmark of cancer, making them a crucial target for cancer immunotherapy. CTAs-targeted antibodies, vaccines, and chimeric antigen receptor-modified T cells (CAR-T) have recently been used in cancer treatment and achieved promising outcomes in the preclinical and early clinical trials. However, the efficacy of current CTA-targeted therapeutics is either moderate or low in cancer therapy. CTA-targeted cancer immunotherapy is facing enormous challenges. Several critical scientific problems need to be resolved: (1) the antigen presentation function of MHC-I protein is usually deficient in cancer patients, so that very low amounts of intracellular CTA epitopes are presented to tumor cell membrane surface, leading to weak immune response and subsequent immunity to CTAs; (2) various immunosuppressive cells are rich in tumor tissues leading to diminished tumor immunity; (3) the tumor tissue microenvironment markedly reduces the efficacy of cancer immunotherapy. In the current review paper, the authors propose new strategies and approaches to overcome the barriers of CTAs-targeted immunotherapy and to develop novel potent immune therapeutics against cancer. Finally, we highlight that the oncogenic CTAs have high tumor specificity and immunogenicity, and are sensible targets for cancer immunotherapy. We predict that CTAs-targeted immunotherapy will bring about breakthroughs in cancer therapy in the near future.
越来越多的证据表明，许多癌症睾丸抗原（CTAs）在各种类型的癌症中特异性过表达，大多数 CTA 是致癌的。致癌 CTA 的过度表达促进了癌发生、癌症转移和耐药性。致癌 CTA 通常与癌症患者的预后不良相关，是癌症的一个重要标志，使其成为癌症免疫治疗的重要靶点。CTA 靶向抗体、疫苗和嵌合抗原受体修饰的 T 细胞（CAR-T）最近已被用于癌症治疗，并在临床前和早期临床试验中取得了有希望的结果。然而，目前 CTA 靶向治疗在癌症治疗中的疗效要么是中等的，要么是低的。CTA 靶向癌症免疫疗法面临着巨大的挑战。有几个关键的科学问题需要解决：（1）MHC-I 蛋白的抗原呈递功能在癌症患者中通常是不足的，因此细胞内 CTA 表位的数量很少呈递到肿瘤细胞膜表面，导致弱免疫反应和随后对 CTA 的免疫；（2）各种免疫抑制细胞在肿瘤组织中丰富，导致肿瘤免疫减弱；（3）肿瘤组织微环境显著降低了癌症免疫疗法的疗效。在本综述论文中，作者提出了克服 CTA 靶向免疫治疗障碍和开发针对癌症的新型有效免疫治疗方法的新策略和方法。最后，我们强调，致癌 CTA 具有高肿瘤特异性和免疫原性，是癌症免疫治疗的敏感靶点。我们预测，CTA 靶向免疫疗法将在不久的将来在癌症治疗中取得突破。
